Mechanisms of action of antithymocyte globulin : T-cell depletion and beyond
TLDR
ATG provides multifaceted immunomodulation paving the way for future applications and suggesting that the use of ATG should be included in the immunosuppression therapeutic armamentarium to help reduce the incidence of organ rejection and GVHD.Abstract:
The success of allogeneic stem cell transplantation and solid-organ transplantation owes much to improvements in the immunosuppressive regimens that prevent graft-versus-host disease (GVHD) or suppress allograft rejection. A better understanding of the immune mechanisms underlying induction of immunological tolerance is the key to successful transplantation. Polyclonal antibodies such as antithymocyte globulins (ATG) have been used for decades. The common belief is that ATG efficacy relies on its capacity to deplete T lymphocytes. The aim of this review is to offer an overview of the recent findings that have been demonstrated in ATG's immunomodulatory activity. The polyclonal nature of ATG is reflected in its diverse effects on the immune system: (1) T-cell depletion in blood and peripheral lymphoid tissues through complement-dependent lysis and T-cell activation and apoptosis; (2) modulation of key cell surface molecules that mediate leukocyte/endothelium interactions; (3) induction of apoptosis in B-cell lineages; (4) interference with dendritic cell functional properties; and (5) induction of regulatory T and natural killer T cells. As a consequence, ATG provides multifaceted immunomodulation paving the way for future applications and suggesting that the use of ATG should be included in the immunosuppression therapeutic armamentarium to help reduce the incidence of organ rejection and GVHD.read more
Citations
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Journal ArticleDOI
Who is the best donor for a related HLA haplotype-mismatched transplant?
Yu Wang,Ying-Jun Chang,Lan-Ping Xu,Kai-Yan Liu,Dai-Hong Liu,Xiao-Hui Zhang,Huan Chen,Wei Han,Yu-Hong Chen,Feng-Rong Wang,Jing-Zhi Wang,Yao Chen,Chen-Hua Yan,Ming-Rui Huo,Dan Li,Xiao-Jun Huang,Xiao-Jun Huang +16 more
TL;DR: The data indicate which HLA haplotype-mismatched related donors are associated with the best transplant outcomes in persons with hematological neoplasms.
Journal ArticleDOI
Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius.
Gérard Socié,Claudia Schmoor,Wolfgang Bethge,Hellmut Ottinger,Matthias Stelljes,Axel R. Zander,Liisa Volin,Tapani Ruutu,Dominik Heim,Rainer Schwerdtfeger,Karin Kolbe,Jiri Mayer,Johan Maertens,Werner Linkesch,Ernst Holler,Vladimir Koza,Martin Bornhäuser,Hermann Einsele,Hans-Jochem Kolb,Hartmut Bertz,Matthias Egger,Olga Grishina,Jürgen Finke +22 more
TL;DR: The addition of ATG-F to standard cyclosporine, methotrexate GVHD prophylaxis lowers the incidence and severity of cGVHD, and the risk of receiving IST without raising the relapse rate.
Journal ArticleDOI
The role of B cells in the pathogenesis of graft-versus-host disease.
TL;DR: Current experimental and clinical evidence for the involvement of B cells in the pathogenesis of acute and chronic GVHD is summarized and the clinical implications for the management of patients undergoing allogeneic stem cell transplantation are discussed.
Journal ArticleDOI
Prophylaxis and treatment of GVHD: EBMT–ELN working group recommendations for a standardized practice
Tapani Ruutu,Alois Gratwohl,T. de Witte,Boris V. Afanasyev,J. F. Apperley,Almalina Bacigalupo,Francesco Dazzi,Peter Dreger,R. F. Duarte,Jürgen Finke,Laurent Garderet,Hildegard T. Greinix,Ernst Holler,Kröger N,Anita Lawitschka,Mohamad Mohty,Arnon Nagler,Jakob Passweg,Olle Ringdén,Gérard Socié,Jorge Sierra,Anna Sureda,Wieslaw Wiktor-Jedrzejczak,Alejandro Madrigal,Dietger Niederwieser +24 more
TL;DR: Recommendations for prophylaxis and treatment of GVHD in the most common allogeneic transplant setting, transplantation from an HLA-identical sibling or unrelated donor for standard risk malignant disease are proposed.
Journal ArticleDOI
Rabbit ATG but not horse ATG promotes expansion of functional CD4+CD25highFOXP3+ regulatory T cells in vitro.
Xingmin Feng,Sachiko Kajigaya,Elena E. Solomou,Keyvan Keyvanfar,Xiuli Xu,Nalini Raghavachari,Peter J. Munson,Thomas M. Herndon,Jichun Chen,Neal S. Young +9 more
TL;DR: It is shown that in vitro culture of normal human peripheral blood mononuclear cells (PBMCs) with a low-dose rATG resulted in marked expansion of functional Treg by converting CD4+CD25- T cells to CD4-CD25+ T cells, and that hATG did not expand but rather decreased Treg.
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